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Cell Stem Cell. 2012 May 4;10(5):570-82. doi: 10.1016/j.stem.2012.03.002. Epub 2012 Apr 26.

Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells.

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  • 1Department of Internal Medicine, Division of Oncology, Section of Stem Cell Biology, Washington University, St Louis, MO 63110, USA.

Abstract

To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. These data suggest that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which "captures" their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22542160
[PubMed - indexed for MEDLINE]
PMCID:
PMC3348423
Free PMC Article

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